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程序性死亡受体-1/程序性死亡配体1抑制剂:胃癌的临床进展与生物标志物探索

Programmed death receptor-1/programmed death-ligand 1 inhibitors: Clinical progress and biomarker exploration in gastric cancer.

作者信息

Shi Jin, Song Xudong, Gao Zihao, Dai Dezhu, Ding Fan, Wu Xu, Dai Wufei, Tao Guoquan

机构信息

Department of Pediatric Surgery, University Children's Hospital Basel, 4031, Basel, Switzerland.

Department of Clinical Research, University of Basel, 4031, Basel, Switzerland.

出版信息

Heliyon. 2024 Oct 4;10(20):e38710. doi: 10.1016/j.heliyon.2024.e38710. eCollection 2024 Oct 30.

Abstract

Gastric cancer is one of the most common malignant tumours, with limited treatment options and poor prognosis in its advanced stages. In recent years, breakthroughs in tumour immunotherapy have led to immune checkpoint inhibitors becoming a new class of clinical oncology drugs. Programmed death receptor-1 (PD-1) and programmed death-ligand 1 (PD-L1) play significant roles in inhibiting T cell responses and tumour immune escape. PD-1/PD-L1 inhibitors can significantly improve the prognosis of patients with advanced gastric cancer. Moreover, the combination of administering PD-1/PD-L1 inhibitors along with chemotherapy, radiotherapy, targeted therapy, and other immunotherapies may further enhance therapeutic efficacy. However, some scientific issues need to be urgently resolved in the immunotherapy of gastric cancer, including the suboptimal efficacy of PD-1/PD-L1 inhibitor monotherapy, high incidence of immune-related adverse events, and the absence of definitive biomarkers for effectively screening treatment-sensitive populations. This article reviews the mechanism of action, therapeutic advances, adverse effects, and putative predictive biomarkers of PD-1/PD-L1 inhibitors in the treatment of advanced gastric cancer.

摘要

胃癌是最常见的恶性肿瘤之一,其晚期治疗选择有限且预后较差。近年来,肿瘤免疫治疗取得突破,免疫检查点抑制剂成为一类新型临床肿瘤药物。程序性死亡受体1(PD-1)和程序性死亡配体1(PD-L1)在抑制T细胞反应和肿瘤免疫逃逸中起重要作用。PD-1/PD-L1抑制剂可显著改善晚期胃癌患者的预后。此外,将PD-1/PD-L1抑制剂与化疗、放疗、靶向治疗及其他免疫治疗联合使用,可能进一步提高治疗效果。然而,胃癌免疫治疗中仍有一些科学问题亟待解决,包括PD-1/PD-L1抑制剂单药治疗效果欠佳、免疫相关不良事件发生率高,以及缺乏有效筛选治疗敏感人群的明确生物标志物。本文综述了PD-1/PD-L1抑制剂治疗晚期胃癌的作用机制、治疗进展、不良反应及潜在预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e5a/11620122/85c7780fdc77/gr1.jpg

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